Modulation of Schlemm's canal endothelial cell stiffness via latrunculin loaded block copolymer micelles.
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| Title: | Modulation of Schlemm's canal endothelial cell stiffness via latrunculin loaded block copolymer micelles. |
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| Authors: | Stack, Trevor1, Vahabikashi, Amir1, Johnson, Mark1,2,3, Scott, Evan1,4,5,6,7 evan.scott@northwestern.edu |
| Source: | Journal of Biomedical Materials Research, Part A. Jul2018, Vol. 106 Issue 7, p1771-1779. 9p. |
| Abstract: | Abstract: Increased stiffness of Schlemm's canal endothelial cells (SC cells) is a major contributing factor to the increased pressure characteristic of primary open‐angle glaucoma. New treatments for glaucoma are being developed using actin depolymerizers and rho kinase inhibitors to address this increased stiffness. However, these agents have off‐target effects and are not as potent as had been hoped. We have developed a micellar nanocarrier assembled from poly(ethylene glycol)‐bl‐poly(propylene sulfide) copolymers capable of encapsulating latrunculin A (Lat A) with the goal of modulating SC cell stiffness. Lat A‐loaded nanocarriers were similar in size and morphology to unloaded poly (ethylene glycol)‐bl‐poly(propylene sulfide) (PEG‐bl‐PPS) micelles, loaded Lat A at 62% encapsulation efficiency, and retained loaded Lat A for at least 22 days. The continued functional activity of Lat A following encapsulation within micelles was verified in murine macrophages, which are known to display decreased endocytosis in response to Lat A‐dependent cytoskeletal disruption. Endocytic inhibition remained unchanged when comparing equal concentrations of micelle‐loaded versus free form Lat A. Uptake of Lat A‐loaded micelles by human SC cells was verified in vitro with no sign of cytotoxicity, and modulation of SC cell stiffness was measured by atomic force microscopy. Lat A‐loaded micelles significantly decreased SC cell stiffness, which resulted in visible changes in cell morphology as observed by confocal microscopy. Our results demonstrate that PEG‐bl‐PPS micelles represent a tunable platform for the controlled intracellular delivery of latrunculin. These self‐assembled polymeric nanobiomaterials may support the rational design and engineering of delivery systems for the treatment of glaucoma. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1771–1779, 2018. [ABSTRACT FROM AUTHOR] |
| Copyright of Journal of Biomedical Materials Research, Part A is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 129952824 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Modulation of Schlemm's canal endothelial cell stiffness via latrunculin loaded block copolymer micelles. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Stack%2C+Trevor%22">Stack, Trevor</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Vahabikashi%2C+Amir%22">Vahabikashi, Amir</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Johnson%2C+Mark%22">Johnson, Mark</searchLink><relatesTo>1,2,3</relatesTo><br /><searchLink fieldCode="AR" term="%22Scott%2C+Evan%22">Scott, Evan</searchLink><relatesTo>1,4,5,6,7</relatesTo><i> evan.scott@northwestern.edu</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+Biomedical+Materials+Research%2C+Part+A%22">Journal of Biomedical Materials Research, Part A</searchLink>. Jul2018, Vol. 106 Issue 7, p1771-1779. 9p. – Name: Abstract Label: Abstract Group: Ab Data: Abstract: Increased stiffness of Schlemm's canal endothelial cells (SC cells) is a major contributing factor to the increased pressure characteristic of primary open‐angle glaucoma. New treatments for glaucoma are being developed using actin depolymerizers and rho kinase inhibitors to address this increased stiffness. However, these agents have off‐target effects and are not as potent as had been hoped. We have developed a micellar nanocarrier assembled from poly(ethylene glycol)‐bl‐poly(propylene sulfide) copolymers capable of encapsulating latrunculin A (Lat A) with the goal of modulating SC cell stiffness. Lat A‐loaded nanocarriers were similar in size and morphology to unloaded poly (ethylene glycol)‐bl‐poly(propylene sulfide) (PEG‐bl‐PPS) micelles, loaded Lat A at 62% encapsulation efficiency, and retained loaded Lat A for at least 22 days. The continued functional activity of Lat A following encapsulation within micelles was verified in murine macrophages, which are known to display decreased endocytosis in response to Lat A‐dependent cytoskeletal disruption. Endocytic inhibition remained unchanged when comparing equal concentrations of micelle‐loaded versus free form Lat A. Uptake of Lat A‐loaded micelles by human SC cells was verified in vitro with no sign of cytotoxicity, and modulation of SC cell stiffness was measured by atomic force microscopy. Lat A‐loaded micelles significantly decreased SC cell stiffness, which resulted in visible changes in cell morphology as observed by confocal microscopy. Our results demonstrate that PEG‐bl‐PPS micelles represent a tunable platform for the controlled intracellular delivery of latrunculin. These self‐assembled polymeric nanobiomaterials may support the rational design and engineering of delivery systems for the treatment of glaucoma. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1771–1779, 2018. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of Biomedical Materials Research, Part A is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1002/jbm.a.36376 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 9 StartPage: 1771 Titles: – TitleFull: Modulation of Schlemm's canal endothelial cell stiffness via latrunculin loaded block copolymer micelles. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Stack, Trevor – PersonEntity: Name: NameFull: Vahabikashi, Amir – PersonEntity: Name: NameFull: Johnson, Mark – PersonEntity: Name: NameFull: Scott, Evan IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 07 Text: Jul2018 Type: published Y: 2018 Identifiers: – Type: issn-print Value: 15493296 Numbering: – Type: volume Value: 106 – Type: issue Value: 7 Titles: – TitleFull: Journal of Biomedical Materials Research, Part A Type: main |
| ResultId | 1 |
